1,721,076 research outputs found
Electrically evoked [3H]GABA release from cerebral cortical cultures: An in vitro approach for studying glutamate-induced neurotoxicity
No full textIn the present study the [3H]GABA release in the rat cerebral cortex primary cultures, kept at rest or electrically stimulated, was measured. In addition, the development of excitotoxic cell damage caused by pretreating the cells for 10 min with increasing glutamate concentrations (10-300 microM) was examined 2 and 24 h after the insult. Cellular injury was quantitatively assessed by measuring the electrically-evoked [3H] GABA release, the [3H] GABA uptake, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide staining. Trains of electrical pulses at different frequencies (2, 5, 10, and 20 Hz) applied to the cultures elicited a [3H]GABA release which was frequency related, Ca++-dependent, and tetrodotoxin sensitive. Either 2 or 24 h after glutamate exposure, the electrically evoked [3H]GABA release was reduced by glutamate in a concentration dependent manner, while [3H]GABA uptake and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide staining appeared less sensitive. The N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and metabotropic receptor antagonists were tested on 100 microM glutamate-exposed cells and a prominent N-methyl-D-aspartate receptor-mediated component was observed. The present findings indicate that the electrically-evoked [3H]GABA release from cerebral cortical cells could represent a useful approach not only to study the spike-triggered neurosecretion but also to the neuronal damage caused by glutamate, as well as to test potential neuroprotective compounds
The muscarinic modulation of [3H]D-aspartate efflux and [Ca2+](i) levels in rat cerebellar granule cells
No full textThe effects of ACh on [3H]D-aspartate efflux and on calcium levels ([Ca2+]i) were studied at the same time in sister cultures of rat cerebellar granule cells stimulated with electrical pulses (5-20 Hz) or depolarized with KCl (15-40 mM). ACh, 0.3-1000 nM, greatly facilitated the 10-Hz-evoked tritium efflux while its effect on 20 mM KCl-evoked efflux was significantly smaller. ACh, 10-1000 nM, enhanced [Ca2+]i levels to a limited extent under both experimental conditions. Therefore, ACh facilitation was evident above all on the electrically evoked [3H]D-aspartate efflux. The ACh-mediated responses depended on the activation of M3-muscarinic receptors since these responses were blocked by 4-DAMP. ACh, 50 microM, reduced the [Ca2+]i plateau, determined by prolonged electrical or KCl stimulation. This effect was due to its action of M2-receptors being blocked by AF-DX 116. In conclusion, at very low concentrations, ACh greatly facilitated the electrically evoked [3H]D-aspartate efflux through M3-receptors, while at a higher concentrations, it inhibited, through M2-receptors, the rise in [Ca2+]i caused by prolonged cell depolarization
Psychotropic Drugs
No full textPsychotropic drugs are relevant in the treatment of many psychiatric disorders and/or symptoms in palliative medicine. This chapter focuses on two important groups of drugs, namely antipsychotics and cannabinoids.
Antipsychotics have evolved in the last 10 years, with the release of new compounds with less side effects and more specific action for the treatment of disorders with psychotic features, including hallucinations, thought disorders and delusion. In palliative medicine these disorders usually include delirium, brief psychotic reactions, psychotic depression, or psychotic disorders due to medical cause (e.g. brain tumors) or drugs (e.g. corticosteroids, chemotherapeutic agents). The treatment include both first generation, called also typical or conventional antipsychotics, and second generation, or atypical antipsychotics. Both are also used in the adjuvant treatment of other symptoms such as nausea and vomiting or pain resisting to conventional intervention. Furthermore, the effectiveness of antispychotics in terminal sedation and in relieving severe, refractory physical symptoms in terminally ill patients has been repeatedly reported.
Cannabinoids have recently come to the attention in medicine for their possible use in several clinical settings, such as mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis and spinal cord injury, cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, due to the modulating activity of the endocannabinoid system
Farmaci del Sistema Nervoso Centrale. Farmaci per il trattamento del Parkinson.
No full textNel capitolo sono elencati i farmaci utilizzati per il trattamento del Morbo di Parkinson
Changes in synaptosomal high affinity choline uptake following electrical stimulation of guinea-pig cortical slices: effect of atropine and physostigmine.
No full textSuperfused guinea-pig cortical slices were electrically stimulated at different frequencies and the changes in acetylcholine (ACh) content measured. Synaptosomes were prepared at the end of the stimulation period and high affinity choline uptake (HACU) rate was measured. 2 The effect of increasing KC1 concentrations was compared on ACh content of the slices and on synaptosomal HACU. 3 Electrical stimulation (2, 5, 10, 20 Hz) elicited a frequency-dependent linear increase in synaptosomal HACU rate and a decrease in ACh content of the slices. 4 The addition of atropine (1.5 x 10(-8) M) to the slices enhanced and that of physostigmine (3 x 10(-5) M) reduced the frequency-dependent increase in HACU rate. Atropine (1.5 x 10(-6) M) not only antagonized the effect of physostigmine, but the HACU rate measured after treatment with both drugs was larger than that found after atropine alone. 5 These results indicate that in the cortical cholinergic nerve endings, depolarization caused by electrical stimulation is coupled with an increase in choline transport which can be modulated by the addition of atropine or physostigmine. Furthermore, within given experimental conditions a linear relationship exists between the reciprocal of ACh content in the slices and synaptosomal HACU
Glutamate regulation of dopamine release in guinea-pig striatal slices
No full textThe effect of L-glutamic acid (L-Glu) on basal and electrically evoked [3H]-dopamine efflux in guinea pig striatal slices was studied. In the presence of magnesium, L-Glu significantly increased spontaneous [3H]-dopamine efflux. This response was unaffected by the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the non-competitive NMDA receptor antagonist, D-5-methyl-10,11, dihydro-5-H-dibenzo-[a,d]-cyclohepten-5,10-imine maleate (MK-801), the glycine antagonist 7-chlorokynurenic acid (7-CL-KYN) and by the metabotropic receptor antagonist (+)-alpha-methyl-4-carboxyphenyl-glycine (alpha-M4CPG) and L-2-amino-3-phosphonopropionic acid (L-AP3). However, the metabotropic glutamate receptor agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD), increased spontaneous [3H]-dopamine efflux, as did L-Glu, and this response was completely counteracted by alpha-M4CPG. In the absence of magnesium, L-Glu induced a concentration-dependent increase in basal [3H]-dopamine efflux, which was prevented by MK-801. In electrically stimulated striatal slices L-Glu, applied 25 min before the stimulation, concentration-dependently increased the [3H]-dopamine efflux both in the presence and in the absence of magnesium. This effect was completely prevented by CNQX, but not by MK-801 or DL-2-amino-5-phosphono-pentanoic acid (AP5). On the contrary, L-Glu, applied during electrical stimulation (2 min) in the absence of Mg2+, increased the [3H]-dopamine efflux to 200%, and this effect was partly counteracted by MK-801. These results provide evidence that different subtypes of excitatory amino acid receptors modulate [3H]-dopamine efflux depending on the functional state (rest or activity) of the nerve endings. The spontaneous [3H]-dopamine efflux appears to be controlled by metabotropic receptors in the presence of Mg2+ and by NMDA receptors in its absence. Conversely, the AMPA/kainate receptors facilitate the electrically evoked [3H]-dopamine efflux in the presence of Mg2+, whereas the NMDA receptors appeared to be operative, in the absence of Mg2+, as long as L-Glu was applied simultaneously with the electrical stimulation
Effect of adenosine, adenosine triphosphate, adenosine deaminase, dipyridamole and aminophylline on acetylcholine release from electrically-stimulated brain slices
No full textThe effect of adenosine on release of acetylcholine (ACh) was investigated in slices of rat cortex perfused with Krebs solution, at rest and during electrical stimulation at frequencies between 0.2 and 20 Hz. Electrical stimulation brought about a linear increase in release of ACh. Adenosine, in concentrations ranging from 1 to 100 microM, reduced in a dose-dependent manner the release of ACh and was more active on the stimulated than on the resting release. However, the fractional reduction by adenosine of stimulated release of ACh did not vary with increasing stimulation rate. Adenosine triphosphate was less active than adenosine in reducing release of ACh. The inhibitory effect of adenosine was antagonized by aminophylline (0.5 mM) and did not occur when the stimulated release of ACh was enhanced by blocking muscarinic autoreceptors with atropine (15 nM). Aminophylline (0.1 and 0.5 mM) itself exerted a biphasic effect on release of ACh, increasing it at rest and during stimulation at low frequencies, and decreasing it at higher stimulation rates. The manipulation of endogenous adenosine concentrations by adding adenosine deaminase or diphyridamole, an inhibitor of adenosine uptake, had little effect on release of ACh. Dipyridamole, (4 microM), only significantly decreased release of ACh at the 20 Hz stimulation rate
Trasmissione catecolaminergica
No full textSono descritti i principi base della trasmissione catecolaminergica ed i recettori adrenergici. Inoltre, sono descritti gli usi terapeutici dei farmaci interagenti con la trasmissione catecolaminergic
Farmaci per il trattamento del Parkinson
No full textSono descritti i meccanismi neuronali alla base del morbo di Parkinson ed i principi base della terapia di tale patologia
Sistemi di trasmissione - trasmissione catecolaminergica.
No full textNel capitolo e' descritte la farmacologia della trasmissione catecolaminergica, con indicazioni delle principali applicazioni terapeutich
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